Design and Enantioselective Synthesis of β-Vinyl Tryptamine Building Blocks for Construction of Privileged Chiral Indole Scaffolds

Abstract

The highly efficient and stereo-specific synthesis of the enantioenriched versatile building blocks—namely, β-vinyltryptamines—by rhodium-catalyzed allylic substitutions of vinylaziridines and indoles is presented. Besides indoles, pyrroles can also serve as competent carbon nucleophiles in the current reaction, which is different from the previous works. To demonstrate the synthetic utility of our method, up to 11 natural product and pharmaceutically relevant chiral indole scaffolds were synthesized in highly efficient reaction sequences. Notably, asymmetric formal synthesis of a potent constrained analogue of MS-245 and a nNOS and 5-HT1B/1D receptor inhibitor are also reported.